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MiR-786 regulation of a fatty-acid elongase contributes to rhythmic calcium-wave initiation in C. elegans.

ABSTRACT: Rhythmic behaviors are ubiquitous phenomena in animals. In C. elegans, defecation is an ultradian rhythmic behavior: every ?50 s a calcium wave initiating in the posterior intestinal cells triggers the defecation motor program that comprises three sequential muscle contractions. Oscillatory calcium signaling is central to the periodicity of defecation. The posteriormost intestinal cells function as the pacemaker for this rhythmic behavior, although it is unclear how the supremacy of these cells for calcium-wave initiation is controlled.We describe how the loss of the mir-240/786 microRNA cluster, which results in arrhythmic defecation, causes ectopic intestinal calcium-wave initiation. mir-240/786 expression in the intestine is restricted to the posterior cells that function as the defecation pacemaker. Genetic data indicate that mir-240/786 functions upstream of the inositol 1,4,5-trisphosphate (IP(3)) receptor. Through rescue analysis, it was determined that miR-786 functions to regulate defecation. Furthermore, we identified elo-2, a fatty-acid elongase with a known role in defecation cycling, as a direct target for miR-786. We propose that the regulation of palmitate levels through repression of elo-2 activity is the likely mechanistic link to defecation.Together, these data indicate that miR-786 confers pacemaker status on posterior intestinal cells for the control of calcium-wave initiation through the regulation of elo-2 and, subsequently, palmitate levels. We propose that a difference in fatty-acid composition in the posterior intestinal cells may alter the activities of membrane proteins, such as IP(3)-receptor or TRPM channels, that control pacemaker activity in the C. elegans intestine.

SUBMITTER: Kemp BJ

PROVIDER: S-EPMC3586602 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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miR-786 regulation of a fatty-acid elongase contributes to rhythmic calcium-wave initiation in C. elegans.

Kemp Benedict J BJ Allman Erik E Immerman Lois L Mohnen Megan M Peters Maureen A MA Nehrke Keith K Abbott Allison L AL

Current biology : CB 20121106 23

<h4>Background</h4>Rhythmic behaviors are ubiquitous phenomena in animals. In C. elegans, defecation is an ultradian rhythmic behavior: every ∼50 s a calcium wave initiating in the posterior intestinal cells triggers the defecation motor program that comprises three sequential muscle contractions. Oscillatory calcium signaling is central to the periodicity of defecation. The posteriormost intestinal cells function as the pacemaker for this rhythmic behavior, although it is unclear how the suprem ...[more]

PMID: 23141108

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Project description:BackgroundΔ6-Desaturase (Fads2) is widely regarded as rate-limiting in the conversion of dietary α-linolenic acid (18:3n-3; ALA) to the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (22:6n-3; DHA). However, increasing dietary ALA or the direct Fads2 product, stearidonic acid (18:4n-3; SDA), increases tissue levels of eicosapentaenoic acid (20:5n-3; EPA) and docosapentaenoic acid (22:5n-3; DPA), but not DHA. These observations suggest that one or more control points must exist beyond ALA metabolism by Fads2. One possible control point is a second reaction involving Fads2 itself, since this enzyme catalyses desaturation of 24:5n-3 to 24:6n-3, as well as ALA to SDA. However, metabolism of EPA and DPA both require elongation reactions. This study examined the activities of two elongase enzymes as well as the second reaction of Fads2 in order to concentrate on the metabolism of EPA to DHA.Methodology/principal findingsThe substrate selectivities, competitive substrate interactions and dose response curves of the rat elongases, Elovl2 and Elovl5 were determined after expression of the enzymes in yeast. The competitive substrate interactions for rat Fads2 were also examined. Rat Elovl2 was active with C(20) and C(22) polyunsaturated fatty acids and this single enzyme catalysed the sequential elongation reactions of EPA→DPA→24:5n-3. The second reaction DPA→24:5n-3 appeared to be saturated at substrate concentrations not saturating for the first reaction EPA→DPA. ALA dose-dependently inhibited Fads2 conversion of 24:5n-3 to 24:6n-3.ConclusionsThe competition between ALA and 24:5n-3 for Fads2 may explain the decrease in DHA levels observed after certain intakes of dietary ALA have been exceeded. In addition, the apparent saturation of the second Elovl2 reaction, DPA→24:5n-3, provides further explanations for the accumulation of DPA when ALA, SDA or EPA is provided in the diet. This study suggests that Elovl2 will be critical in understanding if DHA synthesis can be increased by dietary means.

Dataset Information

MiR-786 regulation of a fatty-acid elongase contributes to rhythmic calcium-wave initiation in C. elegans.

Publications

miR-786 regulation of a fatty-acid elongase contributes to rhythmic calcium-wave initiation in C. elegans.

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